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A PGC1-α-dependent myokine that drives brown-fat-like development of white fat and thermogenesis
Open accessAbstract
Exercise benefits a variety of organ systems in mammals, and some of the best-recognized effects of exercise on muscle are mediated by the transcriptional co-activator PPAR-γ co-activator-1 α (PGC1-α). Here we show in mouse that PGC1-α expression in muscle stimulates an increase in expression of FNDC5, a membrane protein that is cleaved and secreted as a newly identified hormone, irisin. Irisin acts on white adipose cells in culture and in vivo to stimulate UCP1 expression and a broad program of brown-fat-like development. Irisin is induced with exercise in mice and humans, and mildly increased irisin levels in the blood cause an increase in energy expenditure in mice with no changes in movement or food intake. This results in improvements in obesity and glucose homeostasis. Irisin could be therapeutic for human metabolic disease and other disorders that are improved with exercise.
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“When originally described, it was found to exert browning of WAT, increase energy expenditure, improve insulin sensitivity, and induce weight loss, through upregulation of UCP1 in exercised mice overexpressing PGC-1α [57].”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [57]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The myokines irisin [57] and BAIBA [104] have been described to directly induce WAT “browning” both in vitro and in vivo, by upregulating genes involved in mitochondrial biogenesis, FAO, oxidative phosphorylation, and thermogenesis (1).”
From The Role of Exercise in the Interplay between Myokines, Hepatokines, Osteokines, Adipokines, and Modulation of Inflammation for Energy Substrate Redistribution and Fat Mass Loss: A Review (2020) · cites this paper as [57]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“FNDC-5 is known to drive development of brown-fat-like cells in WAT, which enhances lipid metabolism/oxidation via mitochondrial uncoupling protein 1 (UCP-1) activity [12].”
From β-hydroxy-β -methylbutyrate supplementation benefits the effects of resistance training on body fat reduction via increased irisin expression in white adipose tissue (2021) · cites this paper as [12]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, only the irisin precursor FNDC5 was able to promote the differentiation of stromal vascular cells isolated from WAT from beige mice (browning phenomenon; Bostrom et al., 2012).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Bostrom et al., 2012
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Irisin is a myokine that promotes white adipose tissue browning, originally identified through animal studies [38] and subsequently confirmed in humans [39].”
From Exercise-Induced Myokines in Obesity-Related Metabolic Disorders and Cardiovascular Protection: A Narrative Review (2026) · cites this paper as [38]
The cited source says what the claim attributes to it.
In the citing paper
“which is known to upregulate the WAT browning myokines FNDC5-irisin [57], METRNL [274], and BAIBA [104].”
The cited source says what the claim attributes to it.
In the citing paper
“Irisin is stimulated by ‘Peroxisome proliferator-activated receptor-Gamma Coactivator 1α’ (PGC1α), and mediates beneficial metabolic effects through the beiging of white AT [17,49], thereby activating UCP1 and inducing enhanced thermogenesis within the white AT.”
From Optimised Skeletal Muscle Mass as a Key Strategy for Obesity Management (2025) · cites this paper as [49]
The cited source says what the claim attributes to it.
In the citing paper
“Thus, following the characterization of irisin as a myokine capable of activating adipose tissue browning in rodents in response to exercise (Bostrom et al., 2012) the concept that factors secreted by SkM could signal to other organs has grown and developed.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Bostrom et al., 2012
The cited source says what the claim attributes to it.
In the citing paper
“Irisin, formerly called Iris, is a recently identified myokine, released into the circulation by SkM in an exercise-dependent manner.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Bostrom et al., 2012
The cited source says what the claim attributes to it.
In the citing paper
“It is reported to have the ability to convert WAT to BAT, a phenomenon known as browning; a phenotype set of adaptations that results in increasing total energy expenditure (Bostrom et al., 2012).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Bostrom et al., 2012
The cited source says what the claim attributes to it.
In the citing paper
“Five candidate proteins were found to be mediated by PGC-1α in the muscle: IL-15, Fndc5, VEGFβ, Lrg1, and TIMP4.”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Bostrom et al., 2012
The cited source says what the claim attributes to it.
In the citing paper
“Other papers have demonstrated that exercise induces upregulation in skeletal muscle of PGC1α, a transcriptional co-activator of mitochondrial biogenesis and oxidative metabolism in brown adipose tissue and muscle. In muscle, the increase of PGC1α expression stimulates an upregulation of FNDC5, a membrane protein that is cleaved and secreted into the circulation as the myokine irisin [237].”
From Neurotrophic Factor BDNF, Physiological Functions and Therapeutic Potential in Depression, Neurodegeneration and Brain Cancer (2020) · cites this paper as [237]
In the citing paper
“Irisin is a PPARγ-coactivator-1α (PGCα)-dependent myokine that stimulates browning in subcutaneous adipose tissues and induces increased energy expenditure, which improves obesity and IR through the MAPK and ERK pathways [92,93].”
From Sarcopenic obesity, insulin resistance, and their implications in cardiovascular and metabolic consequences (2020) · cites this paper as [92]
In the citing paper
“Irisin is released by skeletal muscles and has been shown to increase thermogenesis and energy expenditure by promoting the browning of subcutaneous adipocytes.”
From Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility (2024) · cites this paper as [88]
In the citing paper
“Moreover, resistance exercise may improve MASLD through muscle-liver crosstalk mediated by a myokine called irisin (88, 89).”
From Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility (2024) · cites this paper as [88]
In the citing paper
“It also exhibits regulatory effects on lipid metabolism in hepatocytes (88).”
From Diet and physical exercise as key players to tackle MASLD through improvement of insulin resistance and metabolic flexibility (2024) · cites this paper as [88]
In the citing paper
“The main and well-described function of irisin is to induce WAT browning and thus UCP-1-dependent mitochondrial uncoupling [206].”
From Mitochondrial Uncoupling: A Key Controller of Biological Processes in Physiology and Diseases (2019) · cites this paper as [206]
In the citing paper
“Thus, whether exercise can brown WAT in humans, especially through an irisin-mediated pathway, remains controversial55,83,84,90.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [84]
In the citing paper
“Transgenic mice that overexpress muscle peroxisome proliferator-activated receptor-γ coactivator 1-α (PGClα) have higher circulating levels of irisin and increased WAT browning than control mice84.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [84]
In the citing paper
“In a mouse model, fibronectin type III domain containing 5 is cleaved in the muscle cell and secreted as irisin, which induces WAT browning to increase energy expenditure and consequently reduce obesity84.”
From Exerkines in health, resilience and disease (2022) · cites this paper as [84]
In the citing paper
“The first paper to describe irisin, a PGC1α-dependent myokine, that drives ‘browning’ of WAT in an animal model”
From Exerkines in health, resilience and disease (2022) · cites this paper as [84]
In the citing paper
“FNDC5 induces thermogenesis and elevates mitochondrial gene expression [131], and resilient mice have increased NAc metabolism [132].”
From The molecular and cellular mechanisms of depression: a focus on reward circuitry (2019) · cites this paper as [131]
In the citing paper
“recent studies have identified secreted proteins that stimulate brown adipocyte thermogenesis and recruit brown (or beige) adipocytes to white adipose tissue [60] [61].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [61]
In the citing paper
“Interestingly, a moderate increase (threefold) in irisin blood levels in mice enhanced energy expenditure and improved obesity and glucose homeostasis ([12](#B12)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [12]
In the citing paper
“Recent landmark studies have identified novel secreted proteins, such as liver FGF21 ([72](#B72)), cardiac natriuretic peptides ([11](#B11)), and irisin ([12](#B12)), that stimulate brown adipocyte thermogenesis.”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [12]
In the citing paper
“Irisin was shown to trigger WAT remodeling by increasing p38 signaling, UCP1 expression, and therefore browning 115, 116.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [115]
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Cites
2 retracted
Wenz, T., Rossi, S. G., Rotundo, R. L., Spiegelman, B. M., & Moraes, C. T. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0911570106 · Cited by 600
Self-citationRetractedBoström, P., Andersson, L. K., Vind, B. F., Håversen, L., Rutberg, M., Wickström, Y., Larsson, E. N. V., Jansson, P., Svensson, M. K. E., Brånemark, R., et al. (2010) · Diabetes · doi:10.2337/db09-1503 · Cited by 44
Self-citationRetractedA Cold-Inducible Coactivator of Nuclear Receptors Linked to Adaptive Thermogenesis
Puigserver, P., Wu, Z., Park, C. W., Graves, R., Wright, M., & Spiegelman, B. M. (1998) · Cell · doi:10.1016/s0092-8674(00)81410-5 · Cited by 3,864
Self-citationLocating proteins in the cell using TargetP, SignalP and related tools
Emanuelsson, O., Brunak, S., von HEIJNE, G., & Nielsen, H. (2007) · Nature Protocols · doi:10.1038/nprot.2007.131 · Cited by 3,215
Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice
Seale, P., Conroe, H. M., Estall, J. L., Kajimura, S., Frontini, A., Ishibashi, J., Cohen, P., Cinti, S., & Spiegelman, B. M. (2010) · Journal of Clinical Investigation · doi:10.1172/jci44271 · Cited by 1,273
Self-citationNew role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure
Tseng, Y.-H., Kokkotou, E., Schulz, T. J., Huang, T. L., Winnay, J. N., Taniguchi, C. M., Tran, T. T., Suzuki, R., Espinoza, D. O., Yamamoto, Y., et al. (2008) · Nature · doi:10.1038/nature07221 · Cited by 1,099
The role of exercise and PGC1α in inflammation and chronic disease
Handschin, C., & Spiegelman, B. M. (2008) · Nature · doi:10.1038/nature07206 · Cited by 1,083
Self-citationSandri, M., Lin, J., Handschin, C., Yang, W., Arany, Z. P., Lecker, S. H., Goldberg, A. L., & Spiegelman, B. M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0607795103 · Cited by 974
Self-citationInitiation of myoblast to brown fat switch by a PRDM16–C/EBP-β transcriptional complex
Kajimura, S., Seale, P., Kubota, K., Lunsford, E., Frangioni, J. V., Gygi, S. P., & Spiegelman, B. M. (2009) · Nature · doi:10.1038/nature08262 · Cited by 703
Self-citationThe SCX/IMAC enrichment approach for global phosphorylation analysis by mass spectrometry
Villén, J., & Gygi, S. P. (2008) · Nature Protocols · doi:10.1038/nprot.2008.150 · Cited by 637
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Liang, J., Wang, H., Zeng, Y., Qu, Y., Liu, Q., Zhao, F., Duan, J., Jiang, Y., Li, S., Ying, J., et al. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0099 · Cited by 87
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Hou, N., Han, F., & Sun, X. (2014) · Clinical Endocrinology · doi:10.1111/cen.12658 · Cited by 86
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Yang, Z., Xu, C., Chen, Y., & Zhao, Q. (2015) · Europe PMC (PubMed Central) · Cited by 86
Neyrinck, A. M., Bindels, L. B., Geurts, L., Hul, M. V., Cani, P. D., & Delzenne, N. M. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.07.008 · Cited by 86
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Wang, J., Li, D., Wang, P., Hu, X., & Chen, F. (2019) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2019.05.001 · Cited by 86
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Bar‐Ziv, R., Bolas, T., & Dillin, A. G. (2020) · EMBO Reports · doi:10.15252/embr.202050094 · Cited by 86
Kuchay, M. S., Martínez‐Montoro, J. I., Kaur, P., Fernández‐García, J. C., & Ramos‐Molina, B. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101696 · Cited by 86
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Sanchis‐Gomar, F., Alis, R., Pareja-Galeano, H., Solá, E., Víctor, V. M., Rocha, M., Hernández‐Mijares, A., & Romagnoli, M. (2014) · Endocrine · doi:10.1007/s12020-014-0170-9 · Cited by 85
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Faienza, M. F., Brunetti, G., Sanesi, L., Colaianni, G., Celi, M., Piacente, L., D’Amato, G., Schipani, E., Colucci, S. C., & Grano, M. (2018) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2018.03.046 · Cited by 85
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Lu, L., Ma, J., Tang, J., Yang, L., Zheng, Q., Chen, S., Gao, E., Ren, J. T., Yang, L., & Yang, J. Z. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.166 · Cited by 84
Park, E. J., Myint, P. K., Ito, A., Appiah, M. G., Darkwah, S. O., Kawamoto, E., & Shimaoka, M. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.588066 · Cited by 84
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Norheim, F., Gjelstad, I., Hjorth, M., Vinknes, K., Langleite, T., Holen, T., Jensen, J., Dalen, K., Karlsen, A., Kielland, A., et al. (2012) · Nutrients · doi:10.3390/nu4121898 · Cited by 83
So, W. Y., & Leung, P. S. (2016) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2016.07.022 · Cited by 83
Oelmann, S., Nauck, M., Völzke, H., Bahls, M., & Friedrich, N. (2016) · PLOS ONE · doi:10.1371/journal.pone.0154319 · Cited by 83
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Myokines, physical activity, insulin resistance and autoimmune diseases
Díaz, B. B., González, D. A., Gannar, F., Pérez, M. C. R., & de León, A. C. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.09.002 · Cited by 82
AlKhairi, I., Cherian, P., Abu-Farha, M., Madhoun, A. A., Nizam, R., Melhem, M., Jamal, M., Al-Sabah, S., Ali, H., Tuomilehto, J., et al. (2019) · Cells · doi:10.3390/cells8101283 · Cited by 82
Year in Diabetes 2012: The Diabetes Tsunami
Sherwin, R. S., & Jastreboff, A. M. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-3487 · Cited by 82
The significance of beige and brown fat in humans
Kiefer, F. W. (2017) · Endocrine Connections · doi:10.1530/ec-17-0037 · Cited by 82
Activation of estrogen receptor alpha induces beiging of adipocytes
Santos, R. D. S., Frank, A. P., de Fátima, L. A., Palmer, B. F., Öz, O. K., & Clegg, D. J. (2018) · Molecular Metabolism · doi:10.1016/j.molmet.2018.09.002 · Cited by 82
Impact of Lipotoxicity on Tissue “Cross Talk” and Metabolic Regulation
Montgomery, M. K., Nardo, W. D., & Watt, M. J. (2019) · Physiology · doi:10.1152/physiol.00037.2018 · Cited by 82
Murawska‐Ciałowicz, E., Wolański, P. M., Zuwała−Jagiełło, J., Feito, Y., Petr, M., Kokštejn, J., Šťastný, P., & Goliński, D. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17103589 · Cited by 82
Wu, F., Li, Z., Cai, M., Xi, Y., Xu, Z., Zhang, Z., Li, H., Zhu, W., & Tian, Z. (2020) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2020.06.038 · Cited by 82
Irisin acts through its integrin receptor in a two-step process involving extracellular Hsp90α
Mu, A., Wales, T. E., Zhou, H., Draga-Coletă, S.-V., Gorgulla, C., Blackmore, K. A., Mittenbühler, M. J., Kim, C. R., Laznik-Bogoslavski, D., Zhang, Q., et al. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.05.008 · Cited by 82
Self-citationPharmacological strategies for targeting BAT thermogenesis
Whittle, A. J., Relat, J., & Vidal‐Puig, A. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.04.004 · Cited by 82
Cui, J. Y., & Klaassen, C. D. (2016) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2016.04.010 · Cited by 82
Siteneski, A., Cunha, M. P., Lieberknecht, V., Pazini, F. L., Gruhn, K., Brocardo, P. S., & Rodrigues, A. L. S. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2018.03.004 · Cited by 82
Tu, W., Qiu, H., Liu, Q., Li, X., Zhao, J.-Z., & Zeng, X. (2018) · Journal of Neuroinflammation · doi:10.1186/s12974-018-1177-6 · Cited by 82
Adipogenesis: A Necessary but Harmful Strategy
Hafidi, M. E., Buelna‐Chontal, M., Sánchez‐Muñoz, F., & Carbó, R. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20153657 · Cited by 82
Bonet, M. L., Ribot, J., Galmés, S., Serra, F. A., & Palou, A. (2020) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2020.158676 · Cited by 82
Crosstalk Between Muscle and Bone Via the Muscle-Myokine Irisin
Colaianni, G., Mongelli, T., Colucci, S. C., Cinti, S., & Grano, M. (2016) · Current Osteoporosis Reports · doi:10.1007/s11914-016-0313-4 · Cited by 81
Self-citationThe role of adipose tissue in cancer-associated cachexia
Vaitkus, J. A., & Celi, F. S. (2016) · Experimental Biology and Medicine · doi:10.1177/1535370216683282 · Cited by 81
Metwally, M., Bayoumi, A., Romero‐Gómez, M., Thabet, K., John, M., Adams, L. A., Huo, X., Aller, R., García‐Monzón, C., Arias, M., et al. (2018) · Journal of Hepatology · doi:10.1016/j.jhep.2018.10.021 · Cited by 81
The “irisin system”: From biological roles to pharmacological and nutraceutical perspectives
Flori, L., Testai, L., & Calderone, V. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118954 · Cited by 81
Xue, Y., Hu, S., Chen, C., He, J., Sun, J., Jin, Y., Zhang, Y., Zhu, G., Shi, Q., & Rui, Y. (2021) · International Journal of Biological Sciences · doi:10.7150/ijbs.63505 · Cited by 81
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McNally, B. D., Griffin, J. L., & Roberts, L. D. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500153 · Cited by 81
Thermogenic Ability of Uncoupling Protein 1 in Beige Adipocytes in Mice
Okamatsu‐Ogura, Y., Fukano, K., Tsubota, A., Uozumi, A., Terao, A., Kimura, K., & Saito, M. (2013) · PLoS ONE · doi:10.1371/journal.pone.0084229 · Cited by 81
During, M. J., Liu, X., Huang, W., Magee, D., Slater, A., McMurphy, T. B., Wang, C., & Cao, L. (2015) · Endocrinology · doi:10.1210/en.2014-1905 · Cited by 81
Waldman, M., Bellner, L., Vanella, L., Schragenheim, J., Sodhi, K., Singh, S. P., Lin, D., Lakhkar, A., Li, J., Hochhauser, E., et al. (2016) · Stem Cells and Development · doi:10.1089/scd.2016.0072 · Cited by 81
Induction of thermogenic adipocytes: molecular targets and thermogenic small molecules
Song, N.-J., Chang, S., Li, D. Y., Villanueva, C. J., & Park, K. W. (2017) · Experimental & Molecular Medicine · doi:10.1038/emm.2017.70 · Cited by 81
Zhao, M., & Chen, X. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.07.010 · Cited by 80
Li, Q., Jia, S., Xu, L., Li, B., & Chen, N. (2019) · Food Science & Nutrition · doi:10.1002/fsn3.1006 · Cited by 80
The serum level of irisin, but not asprosin, is abnormal in polycystic ovary syndrome patients
Chang, C. L., Huang, S. Y., Hsu, Y. C., Chin, T. H., & Soong, Y. K. (2019) · Scientific Reports · doi:10.1038/s41598-019-42061-9 · Cited by 80
Frühbeck, G., Fernández-Quintana, B., Paniagua, M., Hernández‐Pardos, A. W., Valentí, V., Moncada, R., Catalán, V., Becerril, S., Gómez‐Ambrosi, J., Portincasa, P., et al. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154261 · Cited by 80
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Shaikh, S., Lee, E. J., Ahmad, K., Ahmad, S. S., Chun, H.-J., Lim, J. H., Lee, Y., & Choi, I. (2021) · Foods · doi:10.3390/foods10102318 · Cited by 81
Fibronectin type III domain‐containing 5 improves aging‐related cardiac dysfunction in mice
Hu, C., Zhang, X., Hu, M., Teng, T., Yuan, Y., Song, P. K., Kong, C., Xu, S., Ma, Z., & Tang, Q. (2022) · Aging Cell · doi:10.1111/acel.13556 · Cited by 80
Adiponectin reduces thermogenesis by inhibiting brown adipose tissue activation in mice
Qiao, L., Yoo, H. S., Bosco, C., Lee, B., Feng, G., Schaack, J. B., Chi, N., & Shao, J. (2014) · Diabetologia · doi:10.1007/s00125-014-3180-5 · Cited by 80
Endothelial Fatty Acid Transport: Role of Vascular Endothelial Growth Factor B
Hagberg, C. E., Mehlem, A., Falkevall, A., Muhl, L., & Eriksson, U. (2013) · Physiology · doi:10.1152/physiol.00042.2012 · Cited by 81
Role of bone morphogenetic protein 4 in the differentiation of brown fat-like adipocytes
Xue, R., Wan, Y., Zhang, S., Zhang, Q., Ye, H., & Li, Y. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00119.2013 · Cited by 80
Physical Exercise-Induced Myokines in Neurodegenerative Diseases
Lee, B., Shin, M., Park, Y., Won, S.-Y., & Cho, K. S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22115795 · Cited by 79
Can exercise training teach us how to treat Alzheimer's disease?
Huuha, A. M., Norevik, C. S., Moreira, J. B. N., Kobro-Flatmoen, A., Scrimgeour, N., Kivipelto, M., Van Praag, H., Ziaei, M., Sando, S. B., Wisløff, U., et al. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2022.101559 · Cited by 79
Effect of Various Exercise Regimens on Selected Exercise-Induced Cytokines in Healthy People
Domin, R., Dadej, D., Pytka, M., Zybek-Kocik, A., Ruchała, M., & Guzik, P. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18031261 · Cited by 79
Irisin in humans: recent advances and questions for future research
Boström, P., Fernández‐Real, J. M., & Mantzoros, C. S. (2013) · Metabolism · doi:10.1016/j.metabol.2013.11.009 · Cited by 79
Self-citationHuman brown adipose tissue as a target for obesity management; beyond cold‐induced thermogenesis
Loh, R. K. C., Kingwell, B. A., & Carey, A. L. (2017) · Obesity Reviews · doi:10.1111/obr.12584 · Cited by 79
Oxidative Stress, Reductive Stress and Antioxidants in Vascular Pathogenesis and Aging
Mladenov, M. I., Lubomirov, L. T., Grisk, O., Avtanski, D. B., Mitrokhin, V. M., Sazdova, I., Keremidarska‐Markova, M., Danailova, Y., Nikolaev, G., Konakchieva, R., et al. (2023) · Antioxidants · doi:10.3390/antiox12051126 · Cited by 79
Iglesias, P. (2025) · Journal of Clinical Medicine · doi:10.3390/jcm14134490 · Cited by 79
Irisin, a unique non-inflammatory myokine in stimulating skeletal muscle metabolism
Vaughan, R. A., Gannon, N. P., Mermier, C. M., & Conn, C. A. (2015) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-015-0433-9 · Cited by 79
Ringholm, S., Knudsen, J. G., Leick, L., Lundgaard, A., Nielsen, M. M., & Pilegaard, H. (2013) · PLoS ONE · doi:10.1371/journal.pone.0064123 · Cited by 79
Plasma irisin levels predict telomere length in healthy adults
Rana, K. S., Arif, M., Hill, E. J., Aldred, S., Nagel, D. A., Nevill, A. M., Randeva, H. S., Bailey, C. J., Bellary, S., & Brown, J. E. P. (2014) · AGE · doi:10.1007/s11357-014-9620-9 · Cited by 79
Sahin-Efe, A., Upadhyay, J., Ko, B., Dincer, F., Park, K., Migdal, A. L., Vokonas, P., & Mantzoros, C. S. (2017) · Metabolism · doi:10.1016/j.metabol.2017.10.011 · Cited by 79
Ruan, Q., Huang, Y., Yang, L., Ruan, J., Gu, W., Zhang, X., Zhang, Y., Zhang, W., & Yu, Z. (2019) · Peptides · doi:10.1016/j.peptides.2019.01.004 · Cited by 79
Myonectin deletion promotes adipose fat storage and reduces liver steatosis
Little, H. C., Rodriguez, S., Lei, X., Tan, S. Y., Stewart, A. N., Sahagun, A., Sarver, D. C., & William Wong, G. (2019) · The FASEB Journal · doi:10.1096/fj.201900520r · Cited by 78
Metadata
- Authors
- Boström, P., Wu, J., Jedrychowski, M. P., Korde, A., Ye, L., Lo, J. C., Rasbach, K. A., Boström, E. A., Choi, J. H., Long, J. Z., Kajimura, S., Zingaretti, M. C., Vind, B. F., Tu, H., Cinti, S., Højlund, K., Gygi, S. P., & Spiegelman, B. M.
- Affiliations
- Harvard University (US)
- Brigham and Women's Hospital (US)
- University of California, San Francisco (US)
- Marche Polytechnic University (IT)
- Odense University Hospital (DK)
- LakePharma (United States) (US)
- Corresponding author
- Spiegelman, Bruce M.
- ORCID
- Venue
- Nature
- Published
- 2012-01
- Volume
- 481
- Issue
- 7382
- Pages
- 463-468
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC3522098
- OpenAlex
- W2085397620
- Cited by
- 4,810
- References
- 26
- Citations by year
- 2026: 309 · 2025: 347 · 2024: 361 · 2023: 392 · 2022: 453 · 2021: 408 · 2020: 393 · 2019: 331 · 2018: 318 · 2017: 294 · 2016: 275 · 2015: 292 · 2014: 283 · 2013: 229 · 2012: 120
- FWCI
- 198.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- Università Politecnica delle Marche (Università Politecnica delle Marche) (submittedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (K99DK087853, DK54477, R56DK054477, R01DK031405, DK-31405, R01DK061562, R01DK054477, R37DK031405)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Keywords
- irisin, FNDC5, PGC-1α, myokines, brown adipose tissue browning, white adipose tissue, thermogenesis, UCP1, physical activity, energy expenditure, obesity, glucose homeostasis, type 2 diabetes, metabolic disease treatment
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Uncoupling Protein 1, Animals, Adipose Tissue, Brown, Cells, Cultured, Energy Metabolism, Gene Expression Regulation, Hormones, Humans, Insulin Resistance, Ion Channels, Mice, Inbred BALB C, Mice, Transgenic, Obesity, Physical Conditioning, Animal, Plasma, Transcription Factors, Exercise, Trans-Activators, Culture Media, Conditioned, Adipocytes, Cell Respiration, Thermogenesis, Models, Animal, Mitochondrial Proteins, Muscle Cells, Intracellular Signaling Peptides and Proteins, Subcutaneous Fat, Mice, Adipose Tissue, White
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